methyl (2S)-2-piperidinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】25354

【品名】methyl (2S)-2-piperidinecarboxylate

【CA登记号】

【分子式】C₇H₁₃NO₂

【分子量】143.18576

【元素组成】C 58.72% H 9.15% N 9.78% O 22.35%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XIV)

3,4,5-Trimethoxyphenylacetic acid (IX) was alkylated with ethyl iodide in the presence of two equivalents of sodium bis(trimethylsilyl)amide to afford racemic trimethoxyphenylbutyric acid (X). After conversion to the corresponding acid chloride with SOCl2, condensation with (R)-4-benzyl-2-oxazolidinone (XI) in the presence of n-butyllithium gave N-acyloxazolidinone (XII) as a diastereomeric mixture that was separated by column chromatography. The required diastereoisomer was then hydrolyzed with lithium peroxide to provide (S)-2-(3,4,5-trimethoxyphenyl)butyric acid (XIII). Subsequent coupling of (XIII) with methyl (S)-pipecolate (XIV) employing 2-chloro-1-methylpyridinium iodide, followed by ester hydrolysis with LiOH, provided amide (XV). Further DCC-promoted coupling of (XV) to alcohol (VIII) provided (XVI). After acid cleavage of the tert-butyl ester, the resulting carboxylic acid was finally coupled to etylenediamine (XVII) in the presence of 1-benzotriazolyloxy tris(dimethylamino)phosphonium hexafluorophosphate to yield the title compound.

参考文献中间体

合成目标

【1】 Yang, W.; Guo, T.; Keenan, T.P.; Laborde, E.; Holt, D.A. (Ariad Pharmaceuticals Inc.); Synthetic derivs. of rapamycin as multimerizing agents for chimeric proteins with immunophilin-derived domains. JP 2000505475; WO 9731898 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	25348	tert-butyl 2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-hydroxypropyl]phenoxy]acetate		C₂₃H₃₀O₆	详情	详情
(IX)	25349	2-(3,4,5-trimethoxyphenyl)acetic acid	937-52-0	C₁₁H₁₄O₅	详情	详情
(X)	25350	2-(3,4,5-trimethoxyphenyl)butyric acid		C₁₃H₁₈O₅	详情	详情
(XI)	25351	(4R)-4-benzyl-1,3-oxazolidin-2-one; (R)-(+)-4-benzyl-2-oxazolidinone	102029-44-7	C₁₀H₁₁NO₂	详情	详情
(XII)	25352	(4R)-4-benzyl-3-[2-(3,4,5-trimethoxyphenyl)butanoyl]-1,3-oxazolidin-2-one		C₂₃H₂₇NO₆	详情	详情
(XIII)	25353	(2S)-2-(3,4,5-trimethoxyphenyl)butyric acid		C₁₃H₁₈O₅	详情	详情
(XIV)	25354	methyl (2S)-2-piperidinecarboxylate		C₇H₁₃NO₂	详情	详情
(XV)	25355	(2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]-2-piperidinecarboxylic acid		C₁₉H₂₇NO₆	详情	详情
(XVI)	25356	(1R)-1-[3-[2-(tert-butoxy)-2-oxoethoxy]phenyl]-3-(3,4-dimethoxyphenyl)propyl (2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]-2-piperidinecarboxylate		C₄₂H₅₅NO₁₁	详情	详情
(XVII)	14754	ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine	107-15-3	C₂H₈N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Acylation of methyl pipecolinate (I) with methyl oxalyl chloride (II) provides oxamate (III). Subsequent addition of 1,1-dimethylpropylmagnesium chloride (IV) to oxamate (III) gives rise to keto amide (V). The methyl ester group of (V) is then hydrolyzed by means of LiOH, yielding the intermediate carboxylic acid (VI)

参考文献中间体

合成目标

【1】 Hamilton, G.S.; Wu, Y.-Q.; Limburg, D.C.; Wilkinson, D.E.; Vaal ,M.J.; Li, J.-H.; Thomas, C.; Huang, W.; Sauer, H.; Ross, D.T.; Soni, R.; Chen, Y.; Guo, H.; Howorth, P.; Valentine, H.; Liang, S.; Spicer, D.; Fuller, M.; Steiner, J.P; Synthesis of N-glyoxyl prolyl and pipecolyl amides and thioesters and evaluation of their in vitro and in vivo nerve regenerative effects. J Med Chem 2002, 45, 16, 3549.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	25354	methyl (2S)-2-piperidinecarboxylate		C₇H₁₃NO₂	详情	详情
(II)	26971	2-methoxy-2-oxoacetyl chloride	5781-53-3	C₃H₃ClO₃	详情	详情
(III)	60287	methyl 1-[2-(methyloxy)-2-oxoacetyl]-2-piperidinecarboxylate		C₁₀H₁₅NO₅	详情	详情
(IV)	60288	chloro(1,1-dimethylpropyl)magnesium		C₅H₁₁ClMg	详情	详情
(V)	60289	methyl 1-(3,3-dimethyl-2-oxopentanoyl)-2-piperidinecarboxylate		C₁₄H₂₃NO₄	详情	详情
(VI)	60290	1-(3,3-dimethyl-2-oxopentanoyl)-2-piperidinecarboxylic acid		C₁₃H₂₁NO₄	详情	详情

Extended Information